Zosuquidar 3HCl

Catalog No.S1481 Batch:S148103

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Technical Data

Formula

C32H31F2N3O2.3HCl
Molecular Weight 636.99 CAS No. 167465-36-3
Solubility (25°C)* In vitro DMSO 100 mg/mL (156.98 mM)
Water 28 mg/mL (43.95 mM)
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
30%PEG400 0.5%Tween80 5%propylene glycol
30.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Zosuquidar 3HCl is a potent modulator of P-glycoprotein-mediated multi-drug resistance with Ki of 60 nM in a cell-free assay. Phase 3.
Targets
P-gp [1]
(Cell-free assay)
60 nM(Ki)
In vitro LY335979 competitively inhibits equilibrium binding of [3H]vinblastine to Pgp by blocking [3H]azidopine photoaffinity labeling of the Pgp in CEM/VLB100 plasma membranes. [1] LY335979 alone shows the cytotoxicity to drug-sensitive and MDR cell lines with IC50 ranging from 6 μM-16 μM and produces its ability to completely reverse the resistance of the oncolytics (vinblastine, doxorubicin, or etoposide) to the MDR cell lines P388/ADR, MCF7/ADR, 2780AD, or UCLA-P3.003VLB at concentration of 0.1 and 0.5 μM. [1] LY335979 significantly restores drug sensitivity in P-gp-expressing leukemia cell lines including K562/HHT40, K562/HHT90, K562/DOX and HL60/DNR, and enhances the cytotoxicity of anthracyclines (daunorubicin, idarubicin, mitoxantrone) and gemtuzumab ozogamicin (Mylotarg) in primary AML blasts with active P-gp. [2] A latest paper indicates that LY335979 completely inhibits apically directed transport of (Z)-endoxifen in the ABCB1-transduced cells. [3]
In vivo

Protocol (from reference)

Kinase Assay:[1]
  • ATPase Assay

    P-Glycoprotein ATPase activity is measured by the liberation of inorganic phosphate from ATP. The assay is measured in a 96-well plate for 90 min at 37 °C. Membranes (8 μg-10 μg protein) are incubated in a total volume of 100 μL of buffer A containing 5 mM sodium azide, 1 mM ouabain, 1 mM EGTA, 3 mM ATP, an ATP regenerating system composed of 5 mM phosphoenolpyruvate, and 3.6 units/mL pyruvate kinase in the presence and absence of 1 mM sodium vanadate. Pgp-ATPase activity is defined as the vanadate-sensitive portion of the total ATPase activity. Plates are read 3 minutes after the addition of the detection solution. The absorbance is measured at 690 nm by a microtiter dish reader. A phosphate standard curve is used to calculate the μmol of phosphate formed. Samples are measured in triplicate.
Cell Assay:[1]
  • Cell lines

    CEM/VLB100, P388/ADR, MCF7/ADR, 2780AD, and UCLA-P3.OO3VLB cells

  • Concentrations

    0.05 μM to 5 μM

  • Incubation Time

    72 hours

  • Method

    Cell viability is determined using a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction method. Cells are harvested during logarithmic growth phase, and seeded in 96-well plates. The cells are then cultured for 72 hours in the presence of oncolytics with or without modulators. MCF-7 and MCF-7/ADR cells are incubated 24 hours before the addition of the drug with and without the LY335979. LY335979 is prepared as 2 mM DMSO stocks and added to wells to give final concentrations ranging from 0.05 to 5 μM. After 72 hours, 20 μL of freshly prepared 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (5 mg/mL in Dulbecco's PBS) is added to each well and incubated for 4 hours in a 37 °C incubator containing 5% CO2. Cells are pelleted in a Sorvall RT6000B centrifuge, 70 μL of medium is carefully removed from each well, and 100 μL of 2-propanol/0.04 N HC1 is added. Cells are resuspended 5-10 times with a Multipipettor or until no particulate matter is visible. Plates are immediately read on a Titertek Multiskan MCC/340 microplate reader Flow Laboratories with a test wavelength of 570 nm and a reference wavelength of 630 nm. Controls are measured in quadruplicate and modulators are measured in duplicate. Cytotoxicity analyses are also performed using the CeliTiter 96 AQueous assay kit.
Animal Study:[1]
  • Animal Models

    P388 or P388/ADR cells are implanted by i.p. injection into female BDF1 mice.

  • Dosages

    ≤30 mg/kg

  • Administration

    Administered via i.p. and i.v.

Customer Product Validation

Data from [Data independently produced by J Lipid Res, 2014, 10.1194/jlr.M052761]

Data from [Data independently produced by Aquat Toxicol, 2014, 156C, 135-147]

Data from [Pharmacol Res, 2013, 67(1), 79-83]

Data from [Data independently produced by , , Eur J Pharm Sci, 2018, 112:112-121]

Selleck's Zosuquidar 3HCl has been cited by 32 publications

Functional Blood-Brain Barrier Model with Tight Connected Minitissue by Liquid Substrates Culture [ Adv Healthc Mater, 2022, e2201984] PubMed: 36394091
Overcoming Resistance to Anti–Nectin-4 Antibody-Drug Conjugate [ Mol Cancer Ther, 2022, 21 (7): 1227–1235.] PubMed: None
Overcoming Resistance to Anti-nectin-4 Antibody-Drug Conjugate [ Mol Cancer Ther, 2022, molcanther.0013.2022] PubMed: 35534238
Brain endothelial cells metabolize glutamate via glutamate dehydrogenase to replenish TCA-intermediates and produce ATP under hypoglycemic conditions [ J Neurochem, 2021, 157(6):1861-1875] PubMed: 33025588
Heat Shock Protein Inhibitor 17-Allyamino-17-Demethoxygeldanamycin, a Potent Inductor of Apoptosis in Human Glioma Tumor Cell Lines, Is a Weak Substrate for ABCB1 and ABCG2 Transporters [ Pharmaceuticals (Basel), 2021, 14(2)107] PubMed: 33573093
The blood-brain barrier studied in vitro across species [ PLoS One, 2021, 16(3):e0236770] PubMed: 33711041
Characterization of human pregnane X receptor activators identified from a screening of the Tox21 compound library [ Biochem Pharmacol, 2020, S0006-2952(20)30604-3] PubMed: 33333074
Testing of the Survivin Suppressant YM155 in a Large Panel of Drug-Resistant Neuroblastoma Cell Lines. [ Cancers (Basel), 2020, 2;12(3) pii: E577] PubMed: 32131402
Pranlukast Antagonizes CD49f and Reduces Stemness in Triple-Negative Breast Cancer Cells [ Drug Des Devel Ther, 2020, 12;14:1799-1811] PubMed: 32494122
MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes [ Sci Rep, 2020, 10(1):22124] PubMed: 33335181

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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